During the last year, we have generated ROSA26-targetted ES cells and demonstrated that a transgene can be inserted into the ROSA26 locus at high frequency. We have injected the ROSA26-targeted ES cells into mouse blastocysts and obtained chimeric pups. We are currently testing the germline transmission of a targeted ROSA26 allele. We will first establish the homozygous mouse line and will then examine the frequency of transgene integration by injecting Cre and an exchange vector into fertilized eggs. We can then test whether the transgene can be induced in these embryos and adult mice in the absence of tetracycline.